PubMed · 505053
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J C Rubin, J Jones. 1979. Falling-out: a clinical study.. https://doi.org/10.1016/0160-7987(79)90006-1
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BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.
BACKGROUND AND METHODS: Age-standardized and age-specific mortality rates for cancer of the rectum and cancer of the colon were calculated according to race and gender for 1940-1985; age-standardized rates were calculated according to geographic region for 1950-1980. RESULTS: Mortality rates for cancer of the rectum decreased among white and black people of each gender, in most age categories and all regions of the country. Concurrent with this decline, mortality rates for cancer of the colon increased among all race-gender groups except white females, among whom it decreased. CONCLUSIONS: The decline in mortality rates for cancer of the rectum has been largely unappreciated. When deaths occurring from 1940 to 1985 from cancer of the rectum are combined with those from cancer of the colon, mortality rates are increased. However, this combination of sites obscures the divergent trends, which suggest that these cancers have causes that are at least somewhat different.
The relation of age to 5-year relative survival rates was examined for leading sites of cancer resulting in death among 127,554 patients; data from 1978 to 1982 were studied for four areas of the Surveillance, Epidemiology and End Results program of the National Cancer Institute. Overall and stage-stratified relative survival rates declined with advancing patient age for cancer of the lung, prostate, pancreas, bladder, oral cavity, uterus, cervix, ovary, and large bowel (women only). In men, this trend was not explained by age differences in stage of diagnosis, whereas, among women, age was associated with more advanced disease for most sites examined. Although overall survival rates were lower in black patients compared with white patients, the age-survival and age-stage trends were similar in the two racial groups.